Association between EGFR gene mutant protein expression and T790M mutation after first-generation EGFR-TKI treatment...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy is crucial for lung adenocarcinoma patients with EGFR mutations.
• Understanding resistance mechanisms, including T790M mutations, is vital for optimizing treatment strategies.
• This study focuses on stage IV lung adenocarcinoma with positive EGFR gene mutation expression.

Purpose of the Study:

• To evaluate the efficacy of first-generation EGFR-TKIs in stage IV lung adenocarcinoma patients with EGFR mutations.
• To determine the incidence of T790M mutations following resistance to first-generation EGFR-TKIs.
• To investigate the association between EGFR mutant protein expression and T790M mutation development.

Main Methods:

• Tumor tissues from stage IV lung adenocarcinoma patients receiving first-generation EGFR-TKI therapy were analyzed.
• Immunohistochemistry was employed to detect EGFR mutant protein expression.
• Patient follow-up data were collected to assess T790M mutation incidence and progression-free survival (PFS).

Main Results:

• T790M mutation rates after first-generation TKI resistance were 37.93% and 42.50% in EGFR mutation groups.
• In EGFR exon 19 deletion patients, T790M incidence was significantly higher in those with positive EGFR mutant protein expression (63.64%) compared to negative (22.22%).
• Similarly, for L858R mutations, T790M rates were significantly higher in protein-positive (53.57%) versus protein-negative (16.67%) groups.

Conclusions:

• The development of T790M mutations after first-generation EGFR-TKI resistance may be linked to EGFR mutant protein expression.
• These findings highlight the potential role of protein expression levels in predicting T790M development.
• Further research is warranted to explore targeted therapies based on these predictive markers.